Since the successful mapping of the human genome, the read speed of a DNA sequencer (a device that automatically reads base sequences) has been rapidly improved. Even in the fields of molecular biology and medical care, it is expected that the further improvement of the function of a DNA sequencer will lead to successful outcomes in applications to many directions.
As approaches to realize a third-generation DNA sequencer, measurement methods, in which a nanopore device that includes a pore the size of which is almost equal to that of DNA and electrodes on both sides of the pore is used, have drawn much attention (Non-patent Literature 1). To cite an example, there is one of the measurement methods in which bases are slid one by one between electrodes on the both sides of a pore when DNA passes through the pore, and the base sequence is mapped by observing the variation of tunnel current flowing between the electrodes o the both sides of the pore. The feature of this method (referred to as a tunnel current method hereinafter) lies in the fact that the base sequence of DNA can be analyzed without labeling the DNA, that is to say, without using reagents such as enzymes and fluorescent dyes. Therefore, a process for using reagents can be omitted, with the result that it can be expected that the reduction of analysis cost and the improvement of read throughput will be achieved.
Because of improving mechanical strength in the manufacture of a nanopore device, methods, in which semiconductor substrates, semiconductor materials, and semiconductor processes are used, have drawn much attention (Non-patent Literature 2). As one of typical manufacturing methods, as disclosed in “Brian C. Gierhart, et al., “SENSORS AND ACTUATORS” B 132 (2008) 593-600”, there is a method in which an insulating thin film region is deposited on a semiconductor substrate, two electrodes are formed therein, and a pore is formed by irradiating an electron beam between the two electrodes. A microscopic pore with its diameter 10 nm or less can be formed by controlling the energy of the electron beam, an irradiated area, and a current.
The tunnel current method has a problem in that a minute gap has to be provided between a pair of electrodes. According to “Johan Lagerqvist, et al., “NANO LETTERS” (2006) Vol. 6, No. 4 779-782”, it is suggested that, if a gap between electrodes is set to about 1.25 nm, it becomes possible to identifying individual bases. This is because, due to the fact that the diameter of DNA is about 1 nm, if a gap with its width about 1.25 nm is not provided, it is difficult to flow a tunnel current. In patterning using semiconductor processes, it is difficult to fabricate two electrodes that have about 1.25 nm gap therebetween with high accuracy and reproductivity.
In addition, as materials for the electrodes, precious metals such as gold are mainly examined. In the tunnel current method in which the edges of electrodes are exposed, because oxidization of the edges of electrodes decreases the value of the tunnel current significantly, precious metals such as gold atoms that are oxidation resistant are required as materials for the electrodes. Furthermore, because the edges of electrodes are also exposed to a solution, precious metal electrodes such as gold electrodes are required in terms of corrosion resistance. However, because precious metals such as gold atoms are unworkable, these metals are usually not treated in semiconductor processing, and as can be seen from the fact that precious metals are usually treated as metallic pollution sources in the semiconductor line of an LSI semiconductor process, precious metals have low affinities for the semiconductor processing.
In addition, according to “Johan Lagerqvist, et al., “NANO LETTERS” (2006) Vol. 6, No. 4 779-782”, as for the thickness of the electrode, it is indicated that the bases can be identified from one another with an assumption that the edge of the electrode is equal to 3×3 gold atoms. This assumption is adopted in consideration the fact that, because the pitch of each base of DNA is about 0.34 nm, if the thickness of the electrode is larger than 0.34 nm, tunnel currents that flow through plural bases are detected at the same time, and therefore it becomes impossible to measure the base sequence. Generally speaking, however, it is difficult to form an electrode (especially a gold electrode) in the form of a thin film with its thickness 5 nm or below. When a thin film with its thickness 5 nm or below is attempted to be formed, it becomes difficult because a substance, with which the thin film is attempted to be formed, becomes energetically stabler when the substance is in a dot state than in a thin film state. Especially, it is almost impossible to form an electrode of a thin film whose thickness is comparable with the resolution ability of one base (0.34 nm).
Furthermore, a gold electrode is more susceptible to the reposition of atoms and electromigration at the time of voltage application than electrodes made of other metals. Therefore, the accuracy of measurement results is deteriorated due to the fluctuations of gold atoms at the time of detecting tunnel currents.